Evidence map›Paper›PMID 35884919›Full record

ArticleBiomedicines2022

The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma.

Chien-Chi Lu, Hsiao-Chi Tsai, Dong-Ying Yang, Shih-Wei Wang, Ming-Hsui Tsai, Chun-Hung Hua, Kwei-Jing Chen, Michael Yuan-Chien Chen, Ming-Yu Lien, Chih-Hsin Tang

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  6. Analysis of MSX1, RYK, NFκB p65, and CCL4 Proteins andInternational journal of molecular sciences · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Chien-Chi LuDepartment of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan.
Hsiao-Chi TsaiSchool of Medicine, China Medical University, Taichung 404328, Taiwan.
Dong-Ying YangGraduate Institute of Basic Medical Science, China Medical University, Taichung 404328, Taiwan.
Shih-Wei WangInstitute of Biomedical Science, Mackay Medical College, New Taipei City 252005, Taiwan.ORCID 0000-0001-7522-6352
Ming-Hsui TsaiDepartment of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan.
Chun-Hung HuaDepartment of Otorhinolaryngology, China Medical University Hospital, Taichung 404327, Taiwan.
Kwei-Jing ChenSchool of Dentistry, China Medical University, Taichung 404328, Taiwan.
Michael Yuan-Chien ChenSchool of Dentistry, China Medical University, Taichung 404328, Taiwan.
Ming-Yu LienSchool of Medicine, China Medical University, Taichung 404328, Taiwan.
Chih-Hsin TangSchool of Medicine, China Medical University, Taichung 404328, Taiwan.ORCID 0000-0002-7113-8352
China Medical University · TWAsia University · TWKaohsiung Medical University · TW

Funding

China Medical University Hospital DMR-111-023China Medical University Hospital DMR-111-045Ministry of science and Technology in Taiwan MOST 110-2320-B-039-022-MY3
6 · The paper itself

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC.

Indexed as

angiogenesisangiopoietin 2CCL4metastasisoral squamous cell carcinoma

Identifiers

PMID35884919
PMCPMC9313364
OpenAlexW4283830751

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.